T102C polymorphism in the 5HT2A gene and schizophrenia: relation to phenotype and drug response variability

Although genes play a major role in the etiology of schizophrenia, no major genes involved in this disease have been identified. However, several genes with small effect have been reported, though inconsistently, to increase the risk for schizophrenia. Recently, the 5HT2A 2 allele (T102C polymorphis...

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Bibliographic Details
Published in:Journal of psychiatry & neuroscience 1999-03, Vol.24 (2), p.141-146
Main Authors: Joober, R, Benkelfat, C, Brisebois, K, Toulouse, A, Turecki, G, Lal, S, Bloom, D, Labelle, A, Lalonde, P, Fortin, D, Alda, M, Palmour, R, Rouleau, G A
Format: Article
Language:English
Subjects:
Adult
Alleles
Female
Genetics
Humans
Male
Middle Aged
Phenotype
Polymorphism, Genetic
Receptor, Serotonin, 5-HT2A
Receptors, Serotonin - drug effects
Receptors, Serotonin - genetics
Schizophrenia
Schizophrenia - genetics
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Summary:Although genes play a major role in the etiology of schizophrenia, no major genes involved in this disease have been identified. However, several genes with small effect have been reported, though inconsistently, to increase the risk for schizophrenia. Recently, the 5HT2A 2 allele (T102C polymorphism) was reported to be over-represented in patients with schizophrenia. Other reports have found an excess of allele 2(C) only in schizophrenic patients who are resistant to clozapine, not in those who respond to clozapine. In this study, the 5HT2A receptor allele 2 frequencies were compared between 2 groups of patients with schizophrenia (39 responders and 63 nonresponders) based on long-term outcome and response to typical neuroleptics. A control group of 90 healthy volunteers screened for mental disorders was also included. Genotype 2/2 tended to be more frequent in patients with schizophrenia with poor long-term outcome and poor response to typical neuroleptics (Bonferroni corrected p = 0.09). This difference was significant in men (Bonferroni corrected p = 0.054) but not in women. In addition, the age at first contact with psychiatric care was significantly younger in the patients with schizophrenia with genotype 2/2 than in patients with genotype 1/1. These result suggest that the 5HT2A-receptor gene may play a role in a subset of schizophrenia characterized by poor long-term outcome and poor response to neuroleptics.
ISSN:1180-4882
1488-2434